HIV-1 Reverse Transcription: A Brief Overview Focused on Structure–Function Relationships among Molecules Involved in Initiation of the Reaction

An early step in the life cycle of the human immunodeficiency virus type 1 (HIV-1) is reverse transcription of viral RNA into proviral DNA, which can then be integrated into the host cell genome. Reverse transcription is a discontinuous process carried out by the viral encoded reverse transcriptase that displays DNA polymerase activities on RNA and DNA templates as well as an RNase H activity that degrades transcribed RNA. DNA synthesis is initiated by cellular tRNALys3that binds at its 3′-terminus to the complementary primer binding site of the genomic RNA. The initiation of reverse transcription is itself a complex reaction that requires tRNA placement onto viral RNA and the formation of a specific primer/template complex that is recognized by reverse transcriptase. After initiation takes place, the enzyme translocates from the initially bound RNA/RNA duplex into chimeric replication intermediates and finally accommodates newly synthesized DNA/RNA hybrids. This review focuses on structure–function relationships among these various molecules that are involved in the initiation of HIV-1 reverse transcription.